Prostate Artery Embolization With Embosphere Microspheres Compared to TURP for Benign Prostatic Hyperplasia

Prospective, Controlled Investigation of Prostate Artery Embolization With Embosphere Microspheres Compared to Transurethral Resection of the Prostate for the Treatment of Symptomatic Benign Prostatic Hyperplasia

The purpose of this study is to evaluate improvement of symptoms from benign prostatic hyperplasia (BPH) as assessed by the International Prostate Symptom Score (IPSS) for prostatic artery embolization (PAE) using Embosphere Microspheres compared to conventional transurethral resection of the prostate (TURP).

Study Overview

• Status: Terminated
• Conditions: Benign Prostatic Hyperplasia
• Intervention / Treatment: Device: Embosphere Microspheres; Procedure: TURP

Detailed Description

The study will consist of a screening period in which patient eligibility will be determined and baseline assessments performed. Once eligibility is confirmed, patients will be enrolled within 4 weeks of baseline imaging to receive either TURP or PAE with Embosphere Microspheres. After treatment, patients will return for follow-up visits at Months 1, 3, 6, and 12. At each of these visits patients will complete IPSS and IIEF questionnaires and have a physical exam, laboratory assessments (including PSA), a DRE, and a transrectal ultrasound of the prostate. At each visit patients will have a cystoscopy and proctoscopy if medically indicated. Cystoscopy is necessary in all cases of hematuria (injury associated with bleeding). Proctoscopy is necessary in all cases of bleeding per the rectum. An MRI of the prostate will be conducted at the 3 and 12 month visits. Uroflowmetry testing will be performed at the 1 and 12 month visits, and at other visits if medically indicated. MRIs will be assessed by blinded Central Reviewers.

The primary endpoint will be improvement of symptoms from BPH evaluated using the IPSS at 12 months post treatment. Patients will continue to be followed annually for up to 4 additional years. At a minimum, patients will be requested to complete the IPSS and International Index of Erectile Dysfunction (IIEF) questionnaires by telephone, email or mail once per year during this long term follow up period. Patients who are willing to return to the clinic will have a physical exam, MRI of the prostate, digital rectal exam (DRE), transrectal ultrasound of the prostate, PSA, and uroflowmetry testing performed each year. Treatments for LUTS due to BPH after the study treatment and 12 month follow up are complete will be documented during the long term follow up period to the extent possible. This long term follow up data will be summarized and submitted separately from the data for the initial 12 months of this study.

Safety will be evaluated throughout the initial 12 months of the study by assessing adverse events, as well as changes in laboratory values, and findings on physical examination. Concomitant medication usage will be assessed. A follow up ECG will be performed at the 12 month visit.

Patient recruitment is anticipated to take approximately 2 years. Duration of each patient's participation is expected to be 5 years, including a 4 year long term follow up period. The total duration of the study will be approximately 7 years, including long term follow up.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90822
      • Long Beach VA
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Miami, Florida, United States, 33125
      • Miami VA Healthcare System
    • Miami, Florida, United States, 33136
      • University of Miami Hospital
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21207
      • Johns Hopkins Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Patient is age 50 to 79, inclusive
2. Patient has signed informed consent
3. Patient has had lower urinary tract symptoms (LUTS) secondary to BPH for at least 6 months prior to study treatment
4. Patient has a baseline IPSS Score > 13 at baseline
5. Patient has a prostate size of at least 50 grams and not more than 90 grams, measured by MRI
6. Patient has BPH symptoms refractory to medical treatment or for whom medication is contraindicated, not tolerated or refused
7. Patient must be a candidate for TURP

8. Patient must meet one of the following criteria:

   • Baseline Prostate Specific Antigen (PSA) <2.5 ng/mL (no prostate biopsy required)
   • Baseline PSA >2.5 ng/mL and ≤10 ng/mL AND free PSA > 25% of total PSA (no prostate biopsy required)
   • Baseline PSA >2.5 ng/mL and ≤10 ng/mL AND free PSA < 25% of total PSA AND a negative prostate biopsy result (minimum 12 core biopsy)
   • Baseline PSA >10 ng/mL AND a negative prostate biopsy (minimum 12 core biopsy)

Exclusion Criteria:

1. Active urinary tract infection

2. Biopsy proven prostate or bladder cancer, or any cancer other than basal or squamous cell skin cancer

   • The following patients must undergo prostate biopsy with a minimum of 12 cores and have a negative histopathology report to be enrolled in the study:

     • Patients with digital rectal examination (DRE) findings suspicious for prostate cancer
     • Patients with baseline PSA levels > 10 ng/mL
     • Patients with baseline PSA levels >2.5 ng/mL and < 10ng/mL AND free PSA < 25% of total PSA
   • Patients with cystoscopy findings suspicious for bladder cancer must undergo biopsy and have a negative histopathology report to be enrolled in the study
3. Bladder atonia, neurogenic bladder disorder or other neurological disorder that is impacting bladder function (eg multiple sclerosis, Parkinson's disease, spinal cord injuries, etc)
4. Urethral stricture, bladder neck contracture, sphincter abnormalities, urinary obstruction due to causes other than BPH, or other potentially confounding bladder or urethral disease or condition

5. Patient has taken beta blockers, antihistamines, anticonvulsants, or antispasmodics within 1 week of study treatment AND has not been on the same drug dosage for 6 months with a stable voiding pattern

   • Dosage of these medications should not change during study participation unless medically necessary

6. Patient has taken antidepressants, anticholinergics, androgens or gonadotropin-releasing hormonal analogues within 2 months of study treatment AND has not been on the same drug dosage for at least 3 months with a stable voiding pattern
7. Patient has taken 5-alpha reductase inhibitors or alpha blockers within 1 month of study treatment AND has not been on the same drug dosage for at least 3 months with a stable voiding pattern
8. Previous non-medical BPH treatment, including surgery, TURP, needle ablation, microwave or laser therapy, balloon dilation, stent implantation, or any other invasive treatment to the prostate
9. Any known condition that limits catheter-based intervention or is a contraindication to embolization, such as intolerance to a vessel occlusion procedure or severe atherosclerosis.
10. Patient is unable to stop taking anticoagulant, nonsteroidal antiinflammatory drug (NSAID) or anti-platelet therapy for 7 days prior to study treatment
11. Unable to have MRI imaging (eg metal implant including pacemaker, replacement joint, etc)
12. Patient has an asymmetric prostate, with > 20% difference in size between lobes
13. Cardiac condition including congestive heart failure or arrhythmia, uncontrolled diabetes mellitus, significant respiratory disease or known immunosuppression which required hospitalization within the previous 6 months
14. Baseline serum creatinine level > 1.8 mg/dl
15. Known upper tract renal disease
16. Cystolithiasis or chronic hematuria within 3 months prior to study treatment
17. Active prostatitis
18. Previous rectal surgery other than hemorrhoidectomy, or history of rectal disease
19. History of pelvic irradiation or radical pelvic surgery
20. Patient is interested in future fertility
21. Coagulation disturbances not normalized by medical treatment
22. Acute urinary retention requiring an indwelling catheter
23. Known major iliac arterial occlusive disease
24. Allergy to iodinated contrast agents
25. Hypersensitivity to gelatin products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prostate artery embolization (PAE); Prostate artery embolization using Embosphere Microspheres	Device: Embosphere Microspheres
Active Comparator: Transurethral resection of the prostate (TURP); Transurethral Resection of the Prostate (TURP)	Procedure: TURP; Other Names: TURP - Transurethral resection of the prostate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Prostate Symptom Score (IPSS) - Total Score at 12 Months	The International Prostate Symptom Score (I-PSS) is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). Mild is generally less than or equal to 7, moderate is 8-19 and severe is 20-35. Total score was measured at 12 months.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Hospitalization Post Procedure	The duration of hospitalization associated with the procedure will be calculated in hours. T	1 month
Duration of Post Procedure Catheterization	The duration of post procedure catheterization will be calculated in hours.	1 month
Number of Adverse Events Per Patient	Adverse events during the study were predominantly mild. There are over 4 times as many PAE patients as TURP, so the overall incidence rate of events is proportional to the size of the cohort represented. The most common events among patients who underwent embolization were transient dysuria, bladder spasm, hematuria, hematospermia, nausea and fever. The last 2 are typical of post embolic syndrome common to all embolization procedures. The most frequent adverse events for surgery patients were dysuria and hematuria. Events also include non-TEAEs.	Through early termination of study (with less than 25% of subjects completing 12 month follow up)
Number of Patients With Procedure Related Adverse Events	Safety summaries will include the incidence of treatment-emergent adverse events (TEAEs). Treatment-emergent adverse events (TEAEs) are defined as any event that began on or after the date of treatment or worsened in severity or frequency after treatment was initiated. Events worsening in severity should be considered new adverse events. Adverse events recorded on the case report form (CRF) which began prior to treatment will not be included in the summary tables but will be included in the AE data listings.	TEAEs at time of study termination, with less than 25% of subjects completing 12 month follow up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free Prostate Specific Antigen (PSA) at 6 Month Follow up	Free PSA percentage summarized for both groups at 6 months follow up	6 month follow up
Peak Urine Flow Rate (Qmax) at 1 Month	The peak urine flow rate (Qmax) from the urodynamic and uroflowmetry assessments was assessed at 1 month follow up. (Additional timepoints were not assessed due to early termination).	1 month follow-up
International Index of Erectile Function (IIEF)	Erectile Function (Questions 1-5 & 15), score range 0-5, max score = 30 Orgasmic Function (Questions 9-10), score range 0-5, max score = 10 Sexual Desire (Questions 11-12), score range 1-5, max score = 10 Intercourse Satisfaction (Questions 6-8), score range 0-5, max score = 15 Overall Satisfaction (Questions 13-14), score range 1-5, max score = 10 SCORING for erectile dysfunction (Total of Q1-5 and Q15) is interpreted as follows: 1-10: Severe Erectile Dysfunction 11-16: Moderate dysfunction 17-21: Mild to moderate dysfunction 22-25: Mild dysfunction 26-30: No dysfunction For all subscales, higher scores = less dysfunction/dissatisfaction Total IIEF is out of 75	6 months
Mean Prostate Volume, as Determined by MRI	The mean prostate volume as assessed by MRI is summarized at 3 month time point.	3 month follow-up
Post-void Residual Urinary Volume (PVR)	The post void residual volume (PVR) from the urodynamic and uroflowmetry assessments is summarized for both treatment groups at 1 month time point.	1 month follow-up
Total Prostate Specific Antigen (PSA) at 6 Months	Prostate specific antigen (PSA) will be summarized for both treatment groups for 6 month time point	6 months

Collaborators and Investigators

• Sponsor: Merit Medical Systems, Inc.
• Investigators: Principal Investigator: Francisco, Cesar Carnevale, PhD, University of Sao Paolo, Brazil

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: February 8, 2013
• First Submitted That Met QC Criteria: February 11, 2013
• First Posted (Estimate): February 12, 2013

Study Record Updates

• Last Update Posted (Actual): November 11, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: LUTS; Prostate; urinary retention; BPH; Prostatic Hyperplasia; enlarged prostate
• Additional Relevant MeSH Terms: Pathologic Processes; Prostatic Diseases; Prostatic Hyperplasia; Hyperplasia
• Other Study ID Numbers: BPH-P3-12-01; 2012-003446-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No